Name: Donald Stierle
Title: Research Professor
Office: SB 471E
After completing a B.S. in Chemistry at Southern Methodist University, Don Stierle earned a PhD in Chemistry at the University of California at Riverside. Following a two year postdoctoral appointment at Scripps Institution of Oceanography, Don took a position at Montana Tech of the University of Montana as the Organic Chemistry/Biochemistry Professor. Don was a tenured, full professor and in 2000 was unanimously granted Montana Tech’s first endowed chair in Mathematics and the Sciences, the Rose and Anna Busch Professorship, an honor he held until his departure from Tech in 2009. After 29 years of teaching and research at Montana Tech, Don joined the Department of Biomedical and Pharmaceutical Sciences at UM-Missoula as a Research Professor.
The Stierle Research Lab is dedicated to the isolation and structural characterization of compounds with potent, selected biological activity from both macro- and microorganisms. These include both traditional medicinal plants and microbes isolated from unusual ecological niches. We are currently studying two very different populations of microbes: those isolated from an acid mine waste lake in Butte, Montana, and those isolated from the human microbiome. We are also studying the bioactive components of Ayurvedic plants, and the biotransformation of those components by human gut microbes. Whatever the organism, plant or microbe or a combination of the two, it is extracted in organic solvents and a series of bioassays are used to determine the potential biological activities of these extracts. Signal transduction enzyme inhibition assays have been developed to target activity against specific disease conditions. Of particular interest are those diseases with a connection to chronic inflammation. These include many cancers, Alzheimer’s disease and autoimmune disorders. Using enzyme inhibition as a fractionation guide, we have isolated and elucidated several novel molecules that have shown potent, selective activity against specific cancers – ovarian, non-small lung and leukemia -- in the NIH 60 human cell-line assay.
We are also interested in targeting the antibiotic potential of these metabolites. We use a series of standard disk assays to guide the isolation of compounds with antifungal and antibacterial activity. The rising incidence of immunocompromised individuals has generated an array of emerging infectious diseases in critical need of prophylaxis. Of particular interest are those compounds with antifungal activity, as opportunistic mycoses are a growing problem in immunocompromised individuals, including AIDS patients and patients on immunosuppressive therapy. We are also collaborating with Dr. Allen Harmsen at Montana State University in the search for compounds with specific activity against Pneumocystis jirnoveci (formerly carinii). This unusual microbe was formerly classified as a protozoan but is now classified as a fungus. It is the causative agent of Pneumocystis carinii pneumonia, an insidious opportunistic infection in immunocompromised patients.
The Stierle lab is also looking at the potential of the Berkeley Pit Lake microbes to participate in the remediation of this 40 billion gallon acid mine waste lake that graces the northeast corner of Butte, Montana. These efforts have led to the isolation of an unusual yeast that sorbs metals even at pH 2.3.
The Stierle lab has long studied endosymbiotic microbes isolated from marine sponges and the inner bark of trees – notably the Northwest Pacific yew tree. The Stierles found that many compounds reported from sponge extracts might actually have been produced by their microbial symbionts. This work led to the discovery of a unique compound from a Bermudian sponge endosymbiotic bacterium that showed activity against both pathogenic bacteria and the AIDS virus. The Stierles will work with collaborators at UM to determine how this compound affects the AIDS virus.
In the early 90’s The Stierles also searched for a fungal source of the drug taxol (paclitaxel), an anticancer agent which showed promise in clinical trials against refractory breast and ovarian cancers. Unfortunately the source organism of taxol, the northwest Pacific yew tree, had been clear-cut to the point of endangerment and could not supply the growing demands for taxol. It was clear that additional sources of taxol were necessary. Andrea isolated over 300 fungi from the inner bark and needles of yew trees in Montana, Washington, Idaho and Oregon. In 1993, the team published a report of a fungus isolated from the bark of the Pacific yew tree, Taxus brevifolia Nutt, which could produce taxol in de novo fashion. This unique fungus – Taxomyces andreanae - was named after Andrea, its discoverer. The Stierles hope to compare the production of taxol by the tree and the fungus.
Andrea Stierle and Donald Stierle. 2013. Bioprospecting in the Berkeley Pit: the use of signal transduction enzyme inhibition assays to isolate bioactive secondary metabolites from the extremophilic fungi of an acid mine waste lake. In: “Bioactive Natural Products” Atta-Ur-Rahman, Ed.; Elsevier Science Publishers: Amsterdam. In press.
A. Stierle, D. Stierle, T. Girtsman. 2012. Caspase-1 inhibitors from a deep water, acid mine waste extremophilic fungus with specific cytotoxicity towards leukemia cell lines. J. Nat. Prod. 75, 344–350.
D. Stierle, A. Stierle, T. Girtsman, K. McIntyre, J. Nichols. 2012. Caspase-1 and 3 inhibiting drimane sesquiterpenoids from the extremophilic fungus,Penicillium solitum. J. Nat. Prod. 75, 262–266
R. N. Kharwar, A. Mishra, S. K. Gond, A.Stierle*, D.Stierle. 2011. Anticancer compounds derived from fungal endophytes: their importance and future challenges. Nat. Prod. Rep., 28 (7), 1208 – 1228.
D. Stierle, A. Stierle, B. Patacini, K. McIntyre, R. Girtsman, E. Bolstad. 2011. Berkeleyones and related meroterpenes from a deep water acid mine waste fungus that inhibit the production of interleukin 1-β from induced inflammasomes. J. Nat. Prod. 74, 2273–2277.
Andrea A. Stierle, Donald B. Stierle, Briana Patacini, 2008. The berkeleyamides: four new amides from Penicillium rubrum, a deep water acid mine waste fungus. J. Nat. Prod. 71(5), 856-860.
Stierle, D. B.; Stierle, A. A.; Patacini, B. 2007. The berkeleyacetals, three meroterpenes from a deep water acid mine waste Penicillium. J. Nat. Prod. 70(11); 1820-1823.
A. Stierle, D. Stierle, and K. Kelley, 2006. Berkelic Acid, a novel spiroketal with highly specific anti-tumor activity from an acid-mine waste fungal extremophile. 2006. J. Org. Chem. 71: 5357-5360.
Andrea Stierle and Donald Stierle. Bioprospecting in the Berkeley Pit: Bioactive Metabolites from Acid Mine Waste Extremophiles. In: “Bioactive Natural Products”, Volume 32, Atta-Ur-Rahman, Ed.; Elsevier Science Publishers: Amsterdam. 2005.
A. Stierle, D.Stierle, and K.Kemp, 2004. Novel sesquiterpenoid matrix metalloproteinase-3 inhibitors from an acid mine waste extremophile. in August 2004 D.John Faulkner and Paul Scheurer memorial issue of J. Nat. Prod. 67(8): 1392-1395.
D.Stierle, A. Stierle, J.David Hobbs, Janalee Stokken, and J. Clardy. 2004. Berkeleydione and berkeleytrione, new bioactive metabolites from an acid mine organism. Organic Letters 6(6): 1049-1052.